Investigation of simian virus 40 (SV40) and human JC, BK, MC, KI, and WU polyomaviruses in glioma.

The gliomagenesis remains not fully established and their etiological factors still remain obscure. Polyomaviruses were detected and involved in several human tumors. Their potential implication in gliomas has been not yet surveyed in Africa and Arab World. Herein, we investigated the prevalence of six polyomaviruses (SV40, JCPyV, BKPyV, MCPyV, KIPyV, and WUPyV) in 112 gliomas from Tunisian patients. The DNA sequences of polyomaviruses were examined by PCR assays. Viral infection was confirmed by DNA in situ hybridization (ISH) and/or immunohistochemistry (IHC). The relationships between polyomavirus infection and tumor features were evaluated. Specific SV40 Tag, viral regulatory, and VP1 regions were identified in 12 GBM (10.7%). DNA ISH targeting the whole SV40 genome and SV40 Tag IHC confirmed the PCR findings. Five gliomas yielded JCPyV positivity by PCR and DNA ISH (2.7%). However, no BKPyV, KIPyV, and WUPyV DNA sequences were identified in all samples. MCPyV DNA was identified in 30 gliomas (26.8%). For GBM samples, MCPyV was significantly related to patient age (p = 0.037), tumor recurrence (p = 0.024), and SV40 (p = 0.045) infection. No further significant association was identified with the remaining tumor features (p > 0.05) and patient survival (Log Rank, p > 0.05). Our study indicates the presence of SV40, JCPyV, and MCPyV DNA in Tunisian gliomas. Further investigations are required to more elucidate the potential involvement of polyomaviruses in these destructive malignancies.

Investigation of Human Cytomegalovirus and Human Papillomavirus in Glioma.

The study investigated the human cytomegalovirus (HCMV) and human papillomavirus (HPV) in gliomas. A retrospective study was conducted on 112 samples. HCMV was investigated by PCR, in situ hybridization (ISH) and immunohistochemistry. HPV was tested by PCR and DNA ISH. HCMV was identified in 60 gliomas, including 55 GBM. However, RNA ISH and immunohistochemistry failed to detect HCMV positivity. HPV was identified in 44 GBM. No significant relationship was identified between HCMV and HPV and tumour characteristics (p > 0.05). Our findings support the HCMV and HPV presence in gliomas. Further assays are required to more explore the potential efficient antiviral management.

Colorectal Cancer Detection during a Screening Awareness Campaign in a High-Risk Region in Oman.

INTRODUCTION: Colorectal cancer (CRC) constitutes the third most frequently diagnosed cancer in Oman.  This study report the result of a community based screening campaign to promote the early detection and explore the associated risk factors of CRC amongst Omani population. METHODS: We launched a colorectal cancer awareness campaign in Oman's South Ash Sharqiyah Governorate between January and March, 2023. We conducted a stratified random study including 688 adult Omani participants aged over 40 years old. Local Health Centers collected the questionnaire forms. Fecal occult blood tests (FOBTs) were carried out at Local Health Centers; while medical professionals performed the colonoscopy examination in Sur University Hospital. RESULTS: Overall, the screening response rate was 68.8%. The data indicated that 8.1% of the total sample yielded positive FOBTs; of whom, 85.7% were aged 40-59 years old and 67.9% were obese or overweight. Abnormal colonoscopy was reported in 7 participants. One participant had a confirmed CRC of stage I. CONCLUSION: Screening and early detection campaign can have effect and increase the rate of early detection among population in Oman.

Clinicopathological and prognostic significance of DNA mismatch-repair protein expression in gastric adenocarcinoma

Although the significance of DNA mismatch repair (MMR) protein expression in colorectal cancer is well-established, it remains contentious in extra-colorectal cancers and mainly in gastric adenocarcinoma. Data from Africa and Arab world remain limited. This study explored the MMR expression in gastric adenocarcinoma and evaluated its clinicopathological and prognostic signification among Tunisian patients. A retrospective study of 72 gastric adenocarcinomas was carried out. Clinicopathological particularities and patient outcomes were recorded. MMR expression was determined by immunohistochemistry on whole sections of archived material. Survival analysis was realized utilizing the Kaplan-Meier estimates and Log-Rank test. Expression of MMR proteins was observed in 84.7% of gastric adenocarcinoma samples. The 11 remaining samples (15.3%) exhibited an altered pattern of MMR protein. A significant association was identified between deficient MMR expression and advanced age (p = 0.03), intestinal type (p = 0.04) and lymph node metastases (p = 0.04). No other significant relationship was observed with the remaining selected tumor features. Patient survival was significantly associated with lymph node invasion (p = 0.002), distant metastases (p = 0.02) and tumor differentiation (p = 0.03), but not with MMR status (p = 0.83). MMR deficiency was related to advanced-age, intestinal type and nodal metastasis, but not to survival of Tunisian patients with gastric adenocarcinoma. Larger multicenter studies with additional molecular investigation are required to more explore these tumors.

Bien que l'importance de l'expression des protéines de réparation des mésappariements de l'ADN (MMR) dans le cancer colorectal soit bien établie, elle reste controversée dans les cancers extra-colorectaux et principalement dans l'adénocarcinome gastrique. Les données de l'Afrique et du monde arabe restent limitées. Cette étude a exploré l'expression des protéines MMR dans l'adénocarcinome gastrique et a évalué sa signification clinicopathologique et pronostique chez les patients tunisiens. Une étude rétrospective de 72 adénocarcinomes gastriques a été réalisée. Les particularités clinicopathologiques et pronostiques des patients ont été enregistrées. L'expression des protéines MMR a été déterminée par immunohistochimie. L'analyse de survie a été réalisée en utilisant la méthode de Kaplan-Meier et le test Log-Rank. L'expression des protéines MMR a été observée dans 84,7 % des échantillons d'adénocarcinome gastrique. Les 11 cas restants (15,3 %) présentaient un profil d'expression altérée des protéines MMR. Une association significative a été identifiée entre l'expression déficiente de MMR et l'âge avancé (p = 0,03), le type intestinal (p = 0,04) et les métastases ganglionnaires (p = 0,04). Aucune autre relation significative n'a été observée avec les autres caractéristiques tumorales sélectionnées. La survie des patients était significativement associée à l'envahissement des ganglions lymphatiques (Log Rank, p = 0,002), aux métastases à distance (Log Rank, p = 0,02) et à la différenciation tumorale (Log Rank, p = 0,03), mais pas à l'expression de MMR (Log Rank, p = 0,03). Rang, p = 0,83). Le déficit de l'expression des protéines MMR était lié à l'âge avancé, au type intestinal et aux métastases ganglionnaires, mais pas à la survie des patients tunisiens ayant un adénocarcinome gastrique. Des études multicentriques avec des investigations moléculaires supplémentaires sont nécessaires pour explorer davantage le cancer gastrique avec expression déficiente des protéines MMR.

Screening for NLRP7 mutations in familial and sporadic recurrent hydatidiform moles: report of 2 Tunisian families.

A familial or sporadic recurrent hydatidiform mole is a rare autosomal recessive condition that has been associated with biallelic mutations in the nucleotide-binding, leucine-rich repeat, pyrin domain 7 (NLRP7) gene (19q13.42). Cases from different ethnic origins have been reported earlier. Here we report the first Tunisian patients: 2 sisters with homozygous NLRP7 mutations (p.E570X) and 1 sporadic case with no mutation in NLRP7. Our results extend the number of familial recurrent reproductive wastages due to mutations in NLRP7. We suggest that mutations screening of NLRP7 could be proposed more systematically in women with recurrent pathologic pregnancy outcomes of unknown origin. The rare cases with a typical clinical picture, which were not related to NLRP7 mutation as in our sporadic case, should be investigated more to identify the causative gene.

Histopathological diagnosis of strongyloidiasis hyperinfection in Tunisian patient with hodgkin lymphoma: Case report.

INTRODUCTION: Strongyloides stercoralis, an intestinal nematode, is commonly dispersed throughout the tropical and subtropical regions. Strongyloides stercoralis infection typically contributes to an asymptomatic chronic disease which can remain hidden for decades. However, in immunocompromised patients, the hyperinfection can take place, causing high mortality rates. CASE PRESENTATION: A 45 year-old Tunisian women, with heavy medical history, suffering of stage 3 classic Hodgkin lymphoma under treatment; presented with complaints of epigastric pain, nausea, vomiting. Gastroduodenoscopy showed duodenal and gastric erythematous and ulcerated mucosa. Histological assessment showed chronic infiltration with a large amount of eosinophils around numerous helminth forms identified as larvae of Strongyloides stercoralis. CONCLUSION: Early detection of Strongyloides stercoralis infection in immunocompromised patients is life saving and avoids fatality caused by hyperinfection or systemic dissemination. Routine stool examination may be negative, so histopathological identification of the parasite in tissue sections provides the definite diagnosis.

The input of GATA-3 in the identification of parathyroid carcinoma diagnosis: Case report with review of literature.

INTRODUCTION: and Importance: Parathyroid carcinoma is an exceptional cancer, with significant morbidity and mortality, associated with parathyroid hormone (PTH) mediated hypercalcemia. CASE PRESENTATION: We report a case of parathyroid carcinoma with a difficult histological diagnosis. This case illustrates the usefulness of the immunohistochemical marker "GATA-3" in parathyroid differentiation especially in tumours. CLINICAL DISCUSSION: The diagnosis of parathyroid carcinoma is challenging without the knowledge of the clinical information, laboratory finding, and radiographic imaging studies. The immunohistochemistry is useful tool in these cases to identify the parathyroid origin of neoplasia. GATA-3 is a transcription factor that is involved in the embryonic development of the parathyroid glands and in adult parathyroid cell proliferation. CONCLUSION: It is concluded that GATA-3 is a very sensitive and relatively specific immunohistochemical marker for parathyroid differentiation that can assist in the differential diagnosis of parathyroid tumours.

Inhabitual presentation of Sertoli-Leydig cell tumor of the ovary with xeroderma pigmentosum: Case report with review of literature.

INTRODUCTION: Sertoli-Leydig cell tumors (SLCTs) are rare sex-cord stromal tumors of the ovary. Heterologous components may be present, most commonly in the intermediate differentiated and poorly differentiated groups. Because of their scarcity, SLCTs with heterologous differentiation represent a challenge in both diagnosis and management, with limited available experience. PRESENTATION OF CASE: We report a case of a 27-year-old, Tunisian woman, followed in the Dermatology Department since the age of six months for xeroderma pigmentosum, with a history of basal cell carcinoma of the face operated on several times. The patient presented with abdominal pain and bloating associated with a medium abundance ascites on physical exam. Ultrasound showed a large left adnexal mass associated with an elevated cancer antigen 125 on serological exam. The patient underwent unilateral salpingo-oophorectomy with resection of two omental nodules. Microscopic examination concluded to poorly differentiated Sertoli-Leydig tumor with rhabdomyomatous differentiation. Adjuvant chemotherapy was performed and there was no clinical evidence of tumor recurrence during the three years of follow-up. DISCUSSION: SLCTs with rhabdomyomatous differentiation on the setting of xeroderma pigmentosum are exceptional, microscopic diagnosis and management is challenging, considering the tumor scarcity. CONCLUSION: Further case reports and retrospective studies are required to more understand the pathogenesis of SLCTs and to determine their optimal treatment regimen.

The importance of using fine-needle aspiration cytology in the diagnosis of thyroid nodules.

BACKGROUND: Thyroid nodules are common diseases, frequent in middle-aged women; only 5%-30% are malignant. Fine needle aspiration cytology is a simple, rapid and non invasive diagnostic test, performed to predict malignancy and avoid unnecessary surgery.The aim of this study is to evaluate the accuracy of fine needle aspiration in the management of thyroid lesions. MATERIALS AND METHODS: Our study was retrospective, including all cases of thyroid fine needle aspiration between January 2010 and December 2017, which were verified by microscopic examination, Data was obtained from the files of Pathology and ENT Department of Farhat Hached Hospital of Sousse and from nuclear medicine department of Sahloul Hospital of Sousse, Tunisia. RESULTS: A total of 58 cases were studied, the main age was 40 ± 15,57 years and the sex ratio was 0.03 with female predominance. Concordance between fine needle aspiration and histology was seen in 45 cases. The sensitivity was 60% and the specificity was 100%. The negative and positive predictive values were 100 and 92%, respectively. The concordance index Kappa was of 0.67. CONCLUSION: Thyroid fine needle aspiration in experienced hands is an easily performed diagnostic procedure with very little associated risk. It should be performed in suspect nodules for treatment stratification.

Primary adenoid cystic carcinoma of the lung: A case report and literature review.

Primary adenoid cystic carcinoma (ACC) of the lung is an unusual thoracic neoplasm with slow growing and low-grade malignancy. Usually, it is diagnosed at a higher clinical stage and is difficult to resect due to its central location. Herein, we report a 56-year-old man with hemoptysis associated with dyspnea and weight loss lasting for one month. Bronchial fibroscopy highlighted a budding nodular tumor in the left main bronchus. The patient underwent a left pneumonectomy with mediastinal lymphadenomectomy. Microscopic examination showed tumor cells infiltrating the bronchial wall and the cartilage and concluded to an ACC of the left bronchus. Ear, nose, and throat examination as well as cervico-facial magnetic resonance imaging were performed to search a primary salivary gland tumor and were returned without abnormalities. The tumor was classified as a primary ACC of the left bronchus without lymph node metastasis. To avoid their misdiagnosis, ACCs of the lung should be well known by the pathologist and surgeons. Their pathological features may be misleading and referring to a benign lesion, however, the presence of cribriform foci and infiltrative pattern are very suggestive. Although, indolent and slow growing tumor, long-term recurrences are quite frequent, especially in case of unclear surgical margin.

Trends in the incidence of cancer in the Sousse region, Tunisia, 1993-2006.

In this article, we analyzed trends in incidence rates of the major cancer sites for a 14-year period, 1993-2006, in the Sousse region localized in the centre of Tunisia. Five-year age-specific rates, crude incidence rates (CR), world age-standardized rates (ASR), percent change (PC) and annual percent change (APC) were calculated using annual data on population size and its estimated age structure. A total of 6,975 incident cases of cancer were registered, with a male to-female sex ratio of 1.4:1. ASRs showed stable trends (-0.1% in males, and +1.0% in females). The leading cancer sites in rank were lung, breast, lymphoma, colon-rectum, bladder, prostate, leukemia, stomach and cervix uteri. For males, the incidence rates of lung, bladder and prostate cancers remained stable over time. While, cancers of colon-rectum showed a marked increase in incidence (APC: +4.8%; 95% CI: 1.2%, 8.4%) and non-Hodgkin's lymphoma (NHL) showed a notable decline (APC: -4.4%; 95% CI: -8.2, -0.6). For females, cancers of the breast (APC: +2.2%; 95% CI: 0.4%, 4.0%) and corpus uteri (APC: +7.4%; 95% CI: 2.8%, 12.0%) showed a marked increase in incidence during the study period, while the cervix uteri cancer decreased significantly (APC: -6.1%; 95% CI: -9.2%, -3.0%). The results underline the increasing importance of cancer as a cause of mortality and morbidity in Tunisia. Our findings justify the need to develop effective program aiming at the control and prevention of the spread of cancer amongst Tunisian population.

[p16INK4A overexpression is a useful marker for uterine cervix lesions]. / La surexpression de p16 INK4A est un marqueur utile des lésions du col utérin.

The histological criteria of uterine cervix lesions are well known. However, there is a poor diagnostic reproducibility especially concerning low-grade precancerous lesions. Therefore, the aim of our study was to evaluate the utility of p16INK4A overexpression as a surrogate biomarker of precancerous lesions of the uterine cervix. A retrospective study was carried out by the International Center for Research on Cancer, Lyon, on 79 uterine cervix lesions. Specimens included 4 normal tissue samples, 24 benign lesions, 9 low-grade precancerous lesions (CIN1), 40 high-grade precancerous lesions (CIN2-3) and 2 squamous cell carcinomas. Immunohistochemistry was used to find p16INK4A expression. HPV infection was detected by HPV testing. No p16INK4A expression was detected in normal tissues and benign lesions of the uterine cervix. p16INK4A immunolabeling was weak in CIN1 cases (77.8%). Strong and diffuse p16INK4A expression was detected among all precancerous lesions (CIN2-3) and squamous cell carcinomas. p16INK4A overexpression was associated to the CIN grade (p<0.0001) and high-risk HPV infection (p<0.0001). In conclusion, p16INK4A overexpression should be regarded as a surrogate biomarker of precancerous lesions of the uterine cervix. p16INK4A overexpression is useful in reducing the variability during evaluation of suspicious biopsies of the uterine cervix.

Utility of the immunohistochemical analysis of DNA mismatch-repair proteins in endometrial hyperplasia.

The utility of the expression lack of DNA mismatch-repair (MMR) proteins in the detection of Lynch syndrome in endometrial hyperplasia as precursor lesion of endometrial carcinoma has not been well-established. The study investigated the immunoexpression pattern of MMR proteins in endometrial hyperplasia from Tunisian patients. We carried out a retrospective study of 60 endometrial hyperplasias diagnosed among Tunisian patients. Expression of MLH1, MSH2, MSH6, and PMS2 proteins was performed by immunohistochemistry on whole-slide sections of archival tissues. Analysis of MLH1 promoter methylation and microsatellite alterations was conducted in appropriate cases. Microsatellite instability screening was assessed using the Bethesda panel, including BAT25, BAT26, D17S250, D2S123, and D5S346 markers. Expression of MMR proteins was observed in all hyperplasias without atypia as well as in 27 out of 29 atypical hyperplasias. Only two atypical hyperplasias exhibited expression loss of MMR proteins. A single case revealed MSH6 expression lack. Expression loss of MLH1 and PMS2 was identified in another atypical hyperplasia and was associated with hypermethylation of MLH1 promoter. This patient had no familial history of endometrial cancer at the diagnostic time. The two deficient MMR cases showed microsatellite stable pattern. In conclusion, only two endometrial hyperplasias displayed an altered pattern of MMR expression. Our results suggest the limited utility of the immunohistochemical analysis of MMR protein in the early detection of Lynch syndrome in Tunisian patients diagnosed with endometrial hyperplasias. Multicenter studies with larger sample size are needed to more explore these findings.

Significance of p53, p27, Ki-67, E-cadherin, and HER2 expression in upper urinary tract urothelial carcinoma.

BACKGROUND: The study investigated the expression and the clinicopathological significance of p53, p27, Ki-67, E-cadherin, and HER2 in upper urinary tract urothelial carcinomas (UTUC) from Tunisian patients. We performed a retrospective study of 66 UTUC. Main clinicopathological features were reported. The expression of p53, p27, Ki-67, E-cadherin, and HER2 was investigated by immunohistochemistry on whole tissue section. RESULTS: Expression of p53, Ki-67, p27, E-cadherin, and HERE2 was reported in 36.4%, 69.7%, 90.9%, 100%, and 0% of cases, respectively. p53 expression was associated with stage (p = 0.001), positive surgical margin (p = 0.005), and shorter recurrence-free survival (RFS; Log Rank test, p = 0.026). Ki-67 and p27 expression was associated with stage (p < 0.001 and p = 0.001, respectively) and grade (p < 0.001 and p = 0.001, respectively). Using Kaplan-Meier test, the positive surgical margin was associated with shorter RFS compared to free surgical margin (Log Rank test, p = 0.031). Moreover, in univariate Cox regression analysis, surgical margin (p = 0.041; HR 0.325, 95% CI 0.110-0.956) and p53 expression (p = 0.035; HR 0.328, 95% CI 0.116-0.925) were the significant factors associated with RFS. CONCLUSIONS: Together, our findings suggest that positive surgical margin and p53 expression were potential prognostic factors of UTUC since both were associated with shorter RFS in Tunisian patients.

Prognostic significance of MGMT methylation and expression of MGMT, P53, EGFR, MDM2 and PTEN in glioblastoma multiforme.

The study investigated the pattern of MGMT promoter methylation and the expression of MGMT, P53, EGFR, MDM2 and PTEN proteins in glioblastomas multiforme (GBM) and evaluated their prognostic significance. We carried out a retrospective study of 80 GBM. Expression of MGMT as well as of P53, EGFR, MDM2 and PTEN was investigated by immunohistochemistry. MGMT promoter methylation was investigated by methylation specific-PCR of bisulfite-treated DNA. Twenty-five GBM exhibited MGMT expression. Methylation of MGMT promoter was detected in 35.1% of cases. No significant concordance was reported between MGMT promoter methylation and protein expression (κ=-0.047, p=0.11). MGMT promoter methylation was significantly associated only with PTEN expression (p=0.001): no other significant association was identified with clinical parameters as well as with expression of P53, EGFR and MDM2 (p >0.05). Tumor recurrence was significantly associated with unmethylated MGMT promoter (p=0.01) but not with MGMT expression (p=0.51). Recurrence-free survival (RFS) was significantly better among patients with methylated MGMT promoter (log rank, p <0.0001) and PTEN expression (log rank, p=0.025) but not with MGMT expression (log rank, p=0.308). As well, using univariate analysis, MGMT promoter methylation (p=0.001) and PTEN expression (p=0.044) were significantly associated with RFS. In multivariate analysis, only MGMT promoter methylation was significantly associated with RFS (p=0.003). Together, our findings support that MGMT protein expression doesn't reflect the MGMT promoter methylation status. Furthermore, MGMT promoter methylation remains a useful prognostic marker in Tunisian patients with GBM. PTEN expression could be a potential prognostic marker of this tumor.

Extranodal NK/T-cell lymphoma in Tunisia: clinicopathological features, immunophenotype and EBV infection.

BACKGROUND: Extranodal NK/T-cell lymphomas (ENKTL) are rare non-Hodgkin's lymphomas with aggressive clinical behavior. ENKTL are frequently associated with the Epstein-Barr virus (EBV). Data on ENKTL in Africa and Arab world are extremely limited. The study investigated the clinicopathological characteristics, EBV infection, and immunophenotype of ENKTL in Tunisia. We conducted a retrospective study of ENKTL. Main clinicopathological features were reported. The expression of CD3, CD4, CD5, CD8, CD20, CD56, CD57, and Granzyme B were analyzed by immunohistochemistry. EBV infection was detected by IHC (LMP-1) and Epstein-Barr encoding region (EBER1/2) in situ hybridization. RESULTS: A total of nine ENKTL were identified (mean age of 48 years and male-to-female ratio of 8:1). There were five nasal ENKTL, and the remaining four cases had extranasal involvement (palate, sub-mandibular gland, skin, and soft tissues of the ankle). The histopathology showed a lymphoid and pleomorphic proliferation characterized by images of angiocentrism. Strong and diffuse CD3 expression was observed in all cases. Tumor cells exhibited an expression of CD5 (two cases), CD8 (three cases), CD56 (six cases), CD57 (three cases), and Granzyme B (eight cases). All ENKTL cases were EBV-associated. Overall 5-year survival rate was 57%. Although six ENKTL were diagnosed at early clinical stages, the prognosis was unfavorable and associated with patient death in three cases. CONCLUSIONS: ENKTL are exceptional in Tunisia with unfavorable outcome. Histopathological diagnosis remains challenging in clinical practice. However, a careful histopathological examination combined with a correct interpretation of immunohistochemistry and in situ hybridization results refines the ENKTL diagnosis.

Signification of forkhead box A1 (FOXA1) expression in thyroid cancers.

BACKGROUND: Forkhead box A1 (FOXA1) plays an important role in several tumors. This study investigated the potential role of FOXA1 expression in thyroid tumors. We conducted a retrospective study of 110 thyroid lesions and tumors diagnosed during 1995-2018. The expression of FOXA1 was analyzed by immunohistochemistry on archival material. RESULTS: No FOXA1 immunostaining was observed in all cases of Graves' disease, Hashimoto's disease, multi-nodular goiter, and adenoma. FOXA1 expression was absent as well in all papillary and follicular carcinomas, Hurthle cell carcinoma, and undifferentiated sarcoma. Only three anaplastic carcinomas exhibited focally FOXA1 staining. However, FOXA1 was expressed in all medullary carcinomas. No significant correlation was found with all clinicopathological features (p > 0.05 for all). The pattern of FOXA1 staining was similar to that of calcitonin and chromogranin A (p = 0.04 and p = 0.003, respectively). CONCLUSIONS: FOXA1 is expressed mostly in all medullary thyroid carcinomas. Hence, FOXA1 could serve as an additional marker for refining the diagnosis of medullary thyroid carcinoma.

Immunohistochemical analysis of c-erbB-2, Bcl-2, p53, p21WAF1/Cip1, p63 and Ki-67 expression in hydatidiform moles.

Hydatidiform moles (HM) are characterized by an abnormal proliferating trophoblast with a potential for a malignant transformation. Similar to other human tumors, trophoblastic pathogenesis is likely a multistep process involving several molecular and genetic alterations. The study was performed to investigate the expression patterns of c-erbB-2 and Bcl-2 oncoproteins, p53, p21WAF1/CIP1 and p63 tumor suppressor proteins and Ki-67 cell proliferation marker in HM. We conducted a retrospective study of 220 gestational products, including 39 hydropic abortions (HA), 41 partial HM (PHM) and 140 complete HM (CHM). The expression of c-erbB-2, Bcl-2, p53, p21WAF1/CIP1, p63 and Ki-67 was investigated by immunohistochemistry on archival tissues. c-erbB-2 expression was observed in three PHM and 10 CHM. Bcl-2 immunostaining was significantly higher in PHM (61%) and CHM (70.7%) compared with HA (7.7%, p = 0.001 and p < 0.0001, respectively). p53 expression was stronger in CHM (73.6%) compared with PHM (24.4%, p < 0.0001) and HA (12.8%, p < 0.0001). p21WAF1/CIP1 staining was observed as well in molar and non-molar gestations (p > 0.05). p63 immunoexpression was significantly described in CHM (85.7%) and PHM (78%) compared with HA (10.2%, p < 0.0001 and p = 0.0001, respectively). Ki-67 was significantly expressed in CHM (72.1%) compared with HA (46.2%, p = 0.005). Altered expression of Bcl-2, p53, p63 and Ki-67 reflects the HM pathological development. Immunohistochemical analysis is beneficial to recognize the HM molecular and pathogenic mechanisms. Furthermore, it could serve as a useful adjunct to conventional methods for refining HM diagnosis.

Soft tissue leiomyosarcoma-diagnostics, management, and prognosis: Data of the registry cancer of the center of Tunisia.

BACKGROUND: Soft tissue leiomyosarcomas are rare, accounting for almost 5%-10% of all soft tissue sarcomas; they account for almost 1% of all sarcomas. They are aggressive tumors where location, size, and management require a multidisciplinary approach. Since there are few series published, we here analyze epidemiological pattern, clinical and pathologic features of soft tissue leiomyosarcomas. METHODS: We conducted a retrospective study of 29 consecutive cases of histologically proven soft tissue leiomyosarcoma extracted from the database of the Cancer Registry of the Center of Tunisia and the Department of Pathology of Farhat Hached University Hospital of Sousse of Tunisia, during a 10-year period (from January 1996 to December 2005). Epidemiologic details, clinico-pathological features, and treatment modalities were assessed with focus on patients' 5-year overall survival, tumor relapse, and metastases. RESULTS: Soft tissue leiomyosarcoma accounted for 17.5% of all soft tissue sarcomas diagnosed at our pathology department. Most of patients were of advanced age (median: 52 years), with extremes ranging from 12 and 87 years. There was a slight male predominance (sex-ratio = 1.07). Tumors were located mostly in the lower limbs (45%). Deep sites as retroperitoneum was found only in two cases. Tumor size was more than 5 cm in 83% of cases (average size = 9.4 cm). Five cases had metastasis on initial staging. For 24 patients, the disease was locally limited at the moment of diagnosis. Palliative chemotherapy was indicated for four patients and surgery was performed for 20 patients. Local recurrence occurred in 11 patients (55% of operated patients) and metastasis in 6 patients. Overall, 5-year survival was about 24%. CONCLUSION: Our study results highlight the scarcity of soft tissue leiomyosarcoma. Unfortunately, unusual tumor sites, disease's advanced stages, and intralesional resection made the prognosis poorer than in other series. Clinical course of soft tissue leiomyosarcoma was highly marked by local recurrence and metastasis.

HPV infection and p16INK4A and TP53 expression in rare cancers of the uterine cervix.

Cervix cancer remains among most commonly diagnosed cancer in developing countries. Except squamous cell carcinoma and adenocarcinoma, the etiopathology and oncogenic mechanisms of rare cancers remain largely unknown. The study was performed to investigate the value of HPV infection and the expression of p16INK4A and TP53 in rare primitive cancers of the cervix. We conducted a retrospective study of rare primitive cancers of the cervix. Main clinicopathological features were reported. HPV infection was detected by in situ hybridization. Expression of p16INK4A and TP53 was analyzed by immunohistochemistry. Overall, seven cases were identified, including basaloid squamous cell carcinoma (BSCC, n = 2), small cell neuroendocrine carcinoma (SCNEC), granulocytic sarcoma without acute myeloid leukemia, leiomyosarcoma, primitive neuroectodermal tumor and botryoid-type embryonic rhabdomyosarcoma. The mean age of patients was 53.7 years. Four cancers were diagnosed at advanced stages. The prognosis was unfavorable and associated with patient death in five cases. HPV types 16/18 were detected in BSCCs and SCNEC. Strong and diffuse p16INK4A overexpression was described in the nucleus and the cytoplasm of all tumor cells of BSCCs and SCNEC. The remaining cancers exhibited only scattered and focal p16INK4A staining. Mutated TP53 protein was detected in BSCC (case 1) and GS. Rare cancers of the cervix are aggressive and associated with poor prognosis. In contrast to mesenchymal tumors, BSCCs and SCNEC are etiologically related to high-risk HPV infection and could be identified by block positive p16INK4A overexpression as common cancers of the cervix. TP53 mutations are not a negligible genetic event in rare cervical cancers.